ObjectivesAmbulances offer the first opportunity to evaluate hyperacute stroke treatments. In this study, we investigated the conduct of a hyperacute stroke study in the ambulance-based setting with a particular focus on timings and logistics of trial delivery.DesignMulticentre prospective, single-blind, parallel group randomised controlled trial.SettingEight National Health Service ambulance services in England and Wales; 54 acute stroke centres.ParticipantsParamedics enrolled 1149 patients assessed as likely to have a stroke, with Face, Arm, Speech and Time score (2 or 3), within 4 hours of symptom onset and systolic blood pressure >120 mm Hg.InterventionsParamedics administered randomly assigned active transdermal glyceryl trinitrate or sham.Primary and secondary outcomesModified Rankin scale at day 90. This paper focuses on response time intervals, distances travelled and baseline characteristics of patients, compared between ambulance services.ResultsParamedics enrolled 1149 patients between September 2015 and May 2018. Final diagnosis: intracerebral haemorrhage 13%, ischaemic stroke 52%, transient ischaemic attack 9% and mimic 26%. Timings (min) were (median (25–75 centile)): onset to emergency call 19 (5–64); onset to randomisation 71 (45–116); total time at scene 33 (26–46); depart scene to hospital 15 (10–23); randomisation to hospital 24 (16–34) and onset to hospital 97 (71–141). Ambulances travelled (km) 10 (4–19) from scene to hospital. Timings and distances differed between ambulance service, for example, onset to randomisation (fastest 53 min, slowest 77 min; p<0.001), distance from scene to hospital (least 4 km, most 20 km; p<0.001).ConclusionWe completed a large prehospital stroke trial involving a simple-to-administer intervention across multiple ambulance services. The time from onset to randomisation and modest distances travelled support the applicability of future large-scale paramedic-delivered ambulance-based stroke trials in urban and rural locations.Trial registration numberISRCTN26986053.